Tumor Biology

, Volume 37, Issue 9, pp 11633–11643 | Cite as

Noninvasive detection of gastric cancer

  • Qin-Si Wan
  • Kun-He Zhang


Gastric cancer (GC) is the fifth most common cancer and the third common cause of cancer death worldwide. Endoscopy is the most effective method for GC screening, but its application is limited by the invasion. Therefore, continuous efforts have been made to develop noninvasive methods for GC detection and promising results have been reported. Here, we review the advances in GC detection by protein and nucleic acid tumor markers, circulating tumor cells, and tumor-associated autoantibodies in peripheral blood. Some potential new noninvasive methods for GC detection are also reviewed, including exhaled breath analysis, blood spectroscopy analysis and molecular imaging.


Gastric cancer Noninvasive detection Tumor markers Circulating cell-free nucleic acids Exhaled breath analysis Spectroscopy analysis 



This study was supported by the National Natural Science Foundation of China (No. 81560479) and Science and Technology Project of the Education Department of Jiangxi Province (No. KJLD13014).


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer J Int du Cancer. 2015;136(5):E359–86. doi: 10.1002/ijc.29210. CrossRefGoogle Scholar
  2. 2.
    Lu J, Huang CM, Zheng CH, Li P, Xie JW, Wang JB, et al. Consideration of tumor size improves the accuracy of TNM predictions in patients with gastric cancer after curative gastrectomy. Surg Oncol. 2013;22(3):167–71. doi: 10.1016/j.suronc.2013.05.002. PubMedCrossRefGoogle Scholar
  3. 3.
    Choi KS, Jun JK, Park EC, Park S, Jung KW, Han MA, et al. Performance of different gastric cancer screening methods in Korea: a population-based study. PLoS One. 2012;7(11):e50041. doi: 10.1371/journal.pone.0050041. PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Sturgeon CM, Duffy MJ, Hofmann BR, Lamerz R, Fritsche HA, Gaarenstroom K, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem. 2010;56(6):e1–48. doi: 10.1373/clinchem.2009.133124. PubMedCrossRefGoogle Scholar
  5. 5.
    Lam KW, Lo SC. Discovery of diagnostic serum biomarkers of gastric cancer using proteomics. Proteomics Clin Appl. 2008;2(2):219–28. doi: 10.1002/prca.200780015. PubMedCrossRefGoogle Scholar
  6. 6.
    Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer: Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc. 2014;17(1):26–33. doi: 10.1007/s10120-013-0259-5. CrossRefGoogle Scholar
  7. 7.
    Ng EW, Wong MY, Poon TC. Advances in MALDI mass spectrometry in clinical diagnostic applications. Top Curr Chem. 2014;336:139–75. doi: 10.1007/128_2012_413. PubMedCrossRefGoogle Scholar
  8. 8.
    Mateo J, Gerlinger M, Rodrigues DN, de Bono JS. The promise of circulating tumor cell analysis in cancer management. Genome Biol. 2014;15(8):448. doi: 10.1186/s13059-014-0448-5. PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    He CZ, Zhang KH, Li Q, Liu XH, Hong Y, Lv NH. Combined use of AFP, CEA, CA125 and CAl9-9 improves the sensitivity for the diagnosis of gastric cancer. BMC Gastroenterol. 2013;13:87. doi: 10.1186/1471-230x-13-87. PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Yang AP, Liu J, Lei HY, Zhang QW, Zhao L, Yang GH. CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer. Clin Chim Acta; Int J Clin Chem. 2014;437:183–6. doi: 10.1016/j.cca.2014.07.034. CrossRefGoogle Scholar
  11. 11.
    Li Y, Yang Y, Lu M, Shen L. Predictive value of serum CEA, CA19-9 and CA72.4 in early diagnosis of recurrence after radical resection of gastric cancer. Hepato-Gastroenterology. 2011;58(112):2166–70. doi: 10.5754/hge11753. PubMedGoogle Scholar
  12. 12.
    Lai H, Jin Q, Lin Y, Mo X, Li B, He K, et al. Combined use of lysyl oxidase, carcino-embryonic antigen, and carbohydrate antigens improves the sensitivity of biomarkers in predicting lymph node metastasis and peritoneal metastasis in gastric cancer. Tumour Biol: J Int Soc Oncodev Biol Med. 2014;35(10):10547–54. doi: 10.1007/s13277-014-2355-5. CrossRefGoogle Scholar
  13. 13.
    Jiang M, Gu G, Ni B, Wang W, Shi J, Liao P, et al. Detection of serum protein biomarkers by surface enhanced laser desorption/ionization in patients with adenocarcinoma of the lung. Asia Pac J Clin Oncol. 2014;10(2):e7–12. doi: 10.1111/ajco.12057. PubMedCrossRefGoogle Scholar
  14. 14.
    Liu W, Yang Q, Liu B, Zhu Z. Serum proteomics for gastric cancer. Clin Chim Acta; Int J Clin Chem. 2014;431:179–84. doi: 10.1016/j.cca.2014.02.001. CrossRefGoogle Scholar
  15. 15.
    Lu HB, Zhou JH, Ma YY, Lu HL, Tang YL, Zhang QY, et al. Five serum proteins identified using SELDI-TOF-MS as potential biomarkers of gastric cancer. Jpn J Clin Oncol. 2010;40(4):336–42. doi: 10.1093/jjco/hyp175. PubMedCrossRefGoogle Scholar
  16. 16.
    Law KP, Han TL, Tong C, Baker PN. Mass spectrometry-based proteomics for pre-eclampsia and preterm birth. Int J Mol Sci. 2015;16(5):10952–85. doi: 10.3390/ijms160510952. PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Umemura H, Togawa A, Sogawa K, Satoh M, Mogushi K, Nishimura M, et al. Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis. J Gastroenterol. 2011;46(5):577–85. doi: 10.1007/s00535-010-0369-3. PubMedCrossRefGoogle Scholar
  18. 18.
    Subbannayya Y, Mir SA, Renuse S, Manda SS, Pinto SM, Puttamallesh VN, et al. Identification of differentially expressed serum proteins in gastric adenocarcinoma. J Proteome. 2015. doi: 10.1016/j.jprot.2015.04.021. Google Scholar
  19. 19.
    Thaysen-Andersen M, Packer NH. Advances in LC-MS/MS-based glycoproteomics: getting closer to system-wide site-specific mapping of the N- and O-glycoproteome. Biochim Biophys Acta. 2014;1844(9):1437–52. doi: 10.1016/j.bbapap.2014.05.002. PubMedCrossRefGoogle Scholar
  20. 20.
    von Lampe B, Stallmach A, Riecken EO. Altered glycosylation of integrin adhesion molecules in colorectal cancer cells and decreased adhesion to the extracellular matrix. Gut. 1993;34(6):829–36.CrossRefGoogle Scholar
  21. 21.
    Brockhausen I. Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions. EMBO Rep. 2006;7(6):599–604. doi: 10.1038/sj.embor.7400705. PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Xu Y, Zhang L, Hu G. Potential application of alternatively glycosylated serum MUC1 and MUC5AC in gastric cancer diagnosis. Biol: J Int Assoc Biol Stand. 2009;37(1):18–25. doi: 10.1016/j.biologicals.2008.08.002. CrossRefGoogle Scholar
  23. 23.
    Chirwa N, Govender D, Ndimba B, Lotz Z, Tyler M, Panieri E, et al. A 40-50 kDa glycoprotein associated with mucus is identified as alpha-1-acid glycoprotein in carcinoma of the stomach. J Cancer. 2012;3:83–92. doi: 10.7150/jca.3737. PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Kaplan MA, Kucukoner M, Inal A, Urakci Z, Evliyaoglu O, Firat U, et al. Relationship between serum soluble vascular adhesion protein-1 level and gastric cancer prognosis. Oncol Res Treat. 2014;37(6):340–4. doi: 10.1159/000362626. PubMedCrossRefGoogle Scholar
  25. 25.
    Schiel JE. Glycoprotein analysis using mass spectrometry: unraveling the layers of complexity. Anal Bioanal Chem. 2012;404(4):1141–9. doi: 10.1007/s00216-012-6185-2. PubMedCrossRefGoogle Scholar
  26. 26.
    Kolli V, Schumacher KN, Dodds ED. Engaging challenges in glycoproteomics: recent advances in MS-based glycopeptide analysis. Bioanalysis. 2015;7(1):113–31. doi: 10.4155/bio.14.272. PubMedCrossRefGoogle Scholar
  27. 27.
    Lim JB, Kim DK, Chung HW. Clinical significance of serum thymus and activation-regulated chemokine in gastric cancer: potential as a serum biomarker. Cancer Sci. 2014;105(10):1327–33. doi: 10.1111/cas.12505. PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Tas F, Yasasever CT, Karabulut S, Tastekin D, Duranyildiz D. Serum transforming growth factor-beta1 levels may have predictive and prognostic roles in patients with gastric cancer. Tumour Biol: J Int Soc Oncodev Biol Med. 2015;36(3):2097–103. doi: 10.1007/s13277-014-2817-9. CrossRefGoogle Scholar
  29. 29.
    Liu W, Liu B, Xin L, Zhang Y, Chen X, Zhu Z, et al. Down-regulated expression of complement factor I: a potential suppressive protein for gastric cancer identified by serum proteome analysis. Clin Chim Acta; Int J Clin Chem. 2007;377(1–2):119–26. doi: 10.1016/j.cca.2006.09.005. CrossRefGoogle Scholar
  30. 30.
    Chong PK, Lee H, Loh MC, Choong LY, Lin Q, So JB, et al. Upregulation of plasma C9 protein in gastric cancer patients. Proteomics. 2010;10(18):3210–21. doi: 10.1002/pmic.201000127. PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Schiess R, Wollscheid B, Aebersold R. Targeted proteomic strategy for clinical biomarker discovery. Mol Oncol. 2009;3(1):33–44. doi: 10.1016/j.molonc.2008.12.001. PubMedCrossRefGoogle Scholar
  32. 32.
    Chang WC, Hsu PI, Chen YY, Hsiao M, Lu PJ, Chen CH. Observation of peptide differences between cancer and control in gastric juice. Proteomics Clin Appl. 2008;2(1):55–62. doi: 10.1002/prca.200780066. PubMedCrossRefGoogle Scholar
  33. 33.
    Deng K, Lin S, Zhou L, Geng Q, Li Y, Xu M, et al. Three aromatic amino acids in gastric juice as potential biomarkers for gastric malignancies. Anal Chim Acta. 2011;694(1–2):100–7. doi: 10.1016/j.aca.2011.03.053. PubMedCrossRefGoogle Scholar
  34. 34.
    Hsu PI, Chen CH, Hsiao M, Wu DC, Lin CY, Lai KH, et al. Diagnosis of gastric malignancy using gastric juice alpha1-antitrypsin. Cancer Epidemiol, Biomark Prev: Publ Am Assoc Cancer Res, Cosponsored Am Soc Prev Oncol. 2010;19(2):405–11. doi: 10.1158/1055-9965.EPI-09-0609. CrossRefGoogle Scholar
  35. 35.
    Wu W, Chung MC. The gastric fluid proteome as a potential source of gastric cancer biomarkers. J Proteome. 2013;90:3–13. doi: 10.1016/j.jprot.2013.04.035. CrossRefGoogle Scholar
  36. 36.
    Tan S, Liang CR, Yeoh KG, So J, Hew CL, Chung MC. Gastrointestinal fluids proteomics. Proteomics Clin Appl. 2007;1(8):820–33. doi: 10.1002/prca.200700169. PubMedCrossRefGoogle Scholar
  37. 37.
    Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977;37(3):646–50.PubMedGoogle Scholar
  38. 38.
    Chen XQ, Bonnefoi H, Pelte MF, Lyautey J, Lederrey C, Movarekhi S, et al. Telomerase RNA as a detection marker in the serum of breast cancer patients. Clin Cancer Res: Off J Am Assoc Cancer Res. 2000;6(10):3823–6.Google Scholar
  39. 39.
    Zhu W, Qin W, Atasoy U, Sauter ER. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009;2:89. doi: 10.1186/1756-0500-2-89. PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Park JL, Kim HJ, Choi BY, Lee HC, Jang HR, Song KS, et al. Quantitative analysis of cell-free DNA in the plasma of gastric cancer patients. Oncol Lett. 2012;3(4):921–6. doi: 10.3892/ol.2012.592. PubMedPubMedCentralGoogle Scholar
  41. 41.
    Kim K, Shin DG, Park MK, Baik SH, Kim TH, Kim S, et al. Circulating cell-free DNA as a promising biomarker in patients with gastric cancer: diagnostic validity and significant reduction of cfDNA after surgical resection. Ann Surg Treat Res. 2014;86(3):136–42. doi: 10.4174/astr.2014.86.3.136. PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Zheng Y, Chen L, Li J, Yu B, Su L, Chen X, et al. Hypermethylated DNA as potential biomarkers for gastric cancer diagnosis. Clin Biochem. 2011;44(17–18):1405–11. doi: 10.1016/j.clinbiochem.2011.09.006. PubMedCrossRefGoogle Scholar
  43. 43.
    Balgkouranidou I, Karayiannakis A, Matthaios D, Bolanaki H, Tripsianis G, Tentes AA, et al. Assessment of SOX17 DNA methylation in cell free DNA from patients with operable gastric cancer. Association with prognostic variables and survival. Clin Chem Lab Med : CCLM / FESCC. 2013;51(7):1505–10. doi: 10.1515/cclm-2012-0320. CrossRefGoogle Scholar
  44. 44.
    Li M, Izpisua Belmonte JC. Roles for noncoding RNAs in cell-fate determination and regeneration. Nat Struct Mol Biol. 2015;22(1):2–4. doi: 10.1038/nsmb.2946. PubMedCrossRefGoogle Scholar
  45. 45.
    Wang J, Song YX, Ma B, Wang JJ, Sun JX, Chen XW, et al. Regulatory roles of non-coding RNAs in colorectal cancer. Int J Mol Sci. 2015;16(8):19886–919. doi: 10.3390/ijms160819886. PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Kaikkonen MU, Lam MT, Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 2011;90(3):430–40. doi: 10.1093/cvr/cvr097. PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Koturbash I, Zemp FJ, Pogribny I, Kovalchuk O. Small molecules with big effects: the role of the microRNAome in cancer and carcinogenesis. Mutat Res. 2011;722(2):94–105. doi: 10.1016/j.mrgentox.2010.05.006. PubMedCrossRefGoogle Scholar
  48. 48.
    Liu T, Tang H, Lang Y, Liu M, Li X. MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Lett. 2009;273(2):233–42. doi: 10.1016/j.canlet.2008.08.003. PubMedCrossRefGoogle Scholar
  49. 49.
    Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer. 2011;47(5):784–91. doi: 10.1016/j.ejca.2010.10.025. PubMedCrossRefGoogle Scholar
  50. 50.
    Huang D, Wang H, Liu R, Li H, Ge S, Bai M, et al. miRNA27a is a biomarker for predicting chemosensitivity and prognosis in metastatic or recurrent gastric cancer. J Cell Biochem. 2014;115(3):549–56. doi: 10.1002/jcb.24689. PubMedCrossRefGoogle Scholar
  51. 51.
    Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, et al. Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer. Cancer. 2013;119(9):1618–26. doi: 10.1002/cncr.27903. PubMedCrossRefGoogle Scholar
  52. 52.
    Wang Z, Liu M, Zhu H, Zhang W, He S, Hu C, et al. miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS. Mol Carcinog. 2013;52(8):634–46. doi: 10.1002/mc.21899. PubMedCrossRefGoogle Scholar
  53. 53.
    Yang Q, Jie Z, Cao H, Greenlee AR, Yang C, Zou F, et al. Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C. Carcinogenesis. 2011;32(5):713–22. doi: 10.1093/carcin/bgr035. PubMedCrossRefGoogle Scholar
  54. 54.
    Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010;102(7):1174–9. doi: 10.1038/sj.bjc.6605608. PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Li BS, Zhao YL, Guo G, Li W, Zhu ED, Luo X, et al. Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for gastric cancer detection. PLoS One. 2012;7(7):e41629. doi: 10.1371/journal.pone.0041629. PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Li C, Li JF, Cai Q, Qiu QQ, Yan M, Liu BY, et al. MiRNA-199a-3p: a potential circulating diagnostic biomarker for early gastric cancer. J Surg Oncol. 2013;108(2):89–92. doi: 10.1002/jso.23358. PubMedCrossRefGoogle Scholar
  57. 57.
    Zhu C, Ren C, Han J, Ding Y, Du J, Dai N, et al. A five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancer. Br J Cancer. 2014;110(9):2291–9. doi: 10.1038/bjc.2014.119. PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Huarte M. The emerging role of lncRNAs in cancer. Nat Med. 2015;21(11):1253–61. doi: 10.1038/nm.3981. PubMedCrossRefGoogle Scholar
  59. 59.
    Zhou X, Yin C, Dang Y, Ye F, Zhang G. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep. 2015;5:11516. doi: 10.1038/srep11516. PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Dong L, Qi P, MD X, Ni SJ, Huang D, QH X, et al. Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls. Int J Cancer J Int du Cancer. 2015. doi: 10.1002/ijc.29484. Google Scholar
  61. 61.
    Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, et al. Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer. 2014;120(21):3320–8. doi: 10.1002/cncr.28882.PubMedCrossRefGoogle Scholar
  62. 62.
    Damas J, Samuels DC, Carneiro J, Amorim A, Pereira F. Mitochondrial DNA rearrangements in health and disease--a comprehensive study. Hum Mutat. 2014;35(1):1–14. doi: 10.1002/humu.22452. PubMedCrossRefGoogle Scholar
  63. 63.
    Shen J, Platek M, Mahasneh A, Ambrosone CB, Zhao H. Mitochondrial copy number and risk of breast cancer: a pilot study. Mitochondrion. 2010;10(1):62–8. doi: 10.1016/j.mito.2009.09.004. PubMedCrossRefGoogle Scholar
  64. 64.
    Fernandes J, Michel V, Camorlinga-Ponce M, Gomez A, Maldonado C, De Reuse H, et al. Circulating mitochondrial DNA level, a noninvasive biomarker for the early detection of gastric cancer. Cancer Epidemiol, Biomark Prev: Publ Am Assoc Cancer Res, Cosponsored Am Soc Prev Oncol. 2014;23(11):2430–8. doi: 10.1158/1055-9965.EPI-14-0471. CrossRefGoogle Scholar
  65. 65.
    Liao LM, Baccarelli A, Shu XO, Gao YT, Ji BT, Yang G, et al. Mitochondrial DNA copy number and risk of gastric cancer: a report from the shanghai Women’s health study. Cancer Epidemiol, Biomark Prev: Publ Am Assoc Cancer Res, Cosponsored Am Soc Prev Oncol. 2011;20(9):1944–9. doi: 10.1158/1055-9965.EPI-11-0379. CrossRefGoogle Scholar
  66. 66.
    Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014;11(3):145–56. doi: 10.1038/nrclinonc.2014.5. PubMedCrossRefGoogle Scholar
  67. 67.
    Swaminathan R, Butt AN. Circulating nucleic acids in plasma and serum: recent developments. Ann N Y Acad Sci. 2006;1075:1–9. doi: 10.1196/annals.1368.001. PubMedCrossRefGoogle Scholar
  68. 68.
    Gold B, Cankovic M, Furtado LV, Meier F, Gocke CD. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology. J Mol Diagn: JMD. 2015;17(3):209–24. doi: 10.1016/j.jmoldx.2015.02.001. PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Huang JL, Zheng L, Hu YW, Wang Q. Characteristics of long non-coding RNA and its relation to hepatocellular carcinoma. Carcinogenesis. 2014;35(3):507–14. doi: 10.1093/carcin/bgt405. PubMedCrossRefGoogle Scholar
  70. 70.
    Git A, Dvinge H, Salmon-Divon M, Osborne M, Kutter C, Hadfield J, et al. Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA. 2010;16(5):991–1006. doi: 10.1261/rna.1947110. PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    He Y, Lin J, Kong D, Huang M, Xu C, Kim TK, et al. Current state of circulating MicroRNAs as cancer biomarkers. Clin Chem. 2015;61(9):1138–55. doi: 10.1373/clinchem.2015.241190. PubMedCrossRefGoogle Scholar
  72. 72.
    Liu W, Peng B, Lu Y, Xu W, Qian W, Zhang JY. Autoantibodies to tumor-associated antigens as biomarkers in cancer immunodiagnosis. Autoimmun Rev. 2011;10(6):331–5. doi: 10.1016/j.autrev.2010.12.002. PubMedCrossRefGoogle Scholar
  73. 73.
    Gnjatic S, Wheeler C, Ebner M, Ritter E, Murray A, Altorki NK, et al. Seromic analysis of antibody responses in non-small cell lung cancer patients and healthy donors using conformational protein arrays. J Immunol Methods. 2009;341(1–2):50–8. doi: 10.1016/j.jim.2008.10.016. PubMedCrossRefGoogle Scholar
  74. 74.
    Zaenker P, Ziman MR. Serologic autoantibodies as diagnostic cancer biomarkers--a review. Cancer Epidemiol, Biomark Prev: Publ Am Assoc Cancer Res, Cosponsored Am Soc Prev Oncol. 2013;22(12):2161–81. doi: 10.1158/1055-9965.EPI-13-0621. CrossRefGoogle Scholar
  75. 75.
    Tan HT, Low J, Lim SG, Chung MC. Serum autoantibodies as biomarkers for early cancer detection. FEBS J. 2009;276(23):6880–904. doi: 10.1111/j.1742-4658.2009.07396.x. PubMedCrossRefGoogle Scholar
  76. 76.
    Fujiwara S, Wada H, Kawada J, Kawabata R, Takahashi T, Fujita J, et al. NY-ESO-1 antibody as a novel tumour marker of gastric cancer. Br J Cancer. 2013;108(5):1119–25. doi: 10.1038/bjc.2013.51. PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Tsunemi S, Nakanishi T, Fujita Y, Bouras G, Miyamoto Y, Miyamoto A, et al. Proteomics-based identification of a tumor-associated antigen and its corresponding autoantibody in gastric cancer. Oncol Rep. 2010;23(4):949–56.PubMedGoogle Scholar
  78. 78.
    Zhou SL, Ku JW, Fan ZM, Yue WB, Du F, Zhou YF, et al. Detection of autoantibodies to a panel of tumor-associated antigens for the diagnosis values of gastric cardia adenocarcinoma. Dis Esophagus: Off J Int Soc Dis Esophagus / ISDE. 2015;28(4):371–9. doi: 10.1111/dote.12206. CrossRefGoogle Scholar
  79. 79.
    Zayakin P, Ancans G, Silina K, Meistere I, Kalnina Z, Andrejeva D, et al. Tumor-associated autoantibody signature for the early detection of gastric cancer. Int J Cancer J Int du Cancer. 2013;132(1):137–47. doi: 10.1002/ijc.27667. CrossRefGoogle Scholar
  80. 80.
    Saad F, Pantel K. The current role of circulating tumor cells in the diagnosis and management of bone metastases in advanced prostate cancer. Future Oncol. 2012;8(3):321–31. doi: 10.2217/fon.12.3. PubMedCrossRefGoogle Scholar
  81. 81.
    Zhang ZY, Ge HY. Micrometastasis in gastric cancer. Cancer Lett. 2013;336(1):34–45. doi: 10.1016/j.canlet.2013.04.021. PubMedCrossRefGoogle Scholar
  82. 82.
    Alix-Panabieres C, Pantel K. Circulating tumor cells: liquid biopsy of cancer. Clin Chem. 2013;59(1):110–8. doi: 10.1373/clinchem.2012.194258. PubMedCrossRefGoogle Scholar
  83. 83.
    Hiraiwa K, Takeuchi H, Hasegawa H, Saikawa Y, Suda K, Ando T, et al. Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers. Ann Surg Oncol. 2008;15(11):3092–100. doi: 10.1245/s10434-008-0122-9. PubMedCrossRefGoogle Scholar
  84. 84.
    Tinhofer I, Konschak R, Stromberger C, Raguse JD, Dreyer JH, Johrens K, et al. Detection of circulating tumor cells for prediction of recurrence after adjuvant chemoradiation in locally advanced squamous cell carcinoma of the head and neck. Ann Oncol: Off J Eur Soc Med Oncol / ESMO. 2014;25(10):2042–7. doi: 10.1093/annonc/mdu271. CrossRefGoogle Scholar
  85. 85.
    Katoh S, Goi T, Naruse T, Ueda Y, Kurebayashi H, Nakazawa T, et al. Cancer stem cell marker in circulating tumor cells: expression of CD44 variant exon 9 is strongly correlated to treatment refractoriness, recurrence and prognosis of human colorectal cancer. Anticancer Res. 2015;35(1):239–44.PubMedGoogle Scholar
  86. 86.
    Tang L, Zhao S, Liu W, Parchim NF, Huang J, Tang Y, et al. Diagnostic accuracy of circulating tumor cells detection in gastric cancer: systematic review and meta-analysis. BMC Cancer. 2013;13:314. doi: 10.1186/1471-2407-13-314. PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Uenosono Y, Arigami T, Kozono T, Yanagita S, Hagihara T, Haraguchi N, et al. Clinical significance of circulating tumor cells in peripheral blood from patients with gastric cancer. Cancer. 2013;119(22):3984–91. doi: 10.1002/cncr.28309. PubMedCrossRefGoogle Scholar
  88. 88.
    Wang S, Zheng G, Cheng B, Chen F, Wang Z, Chen Y, et al. Circulating tumor cells (CTCs) detected by RT-PCR and its prognostic role in gastric cancer: a meta-analysis of published literature. PLoS One. 2014;9(6):e99259. doi: 10.1371/journal.pone.0099259. PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Huang X, Gao P, Sun J, Chen X, Song Y, Zhao J, et al. Clinicopathological and prognostic significance of circulating tumor cells in patients with gastric cancer: a meta-analysis. Int J Cancer J Int du Cancer. 2015;136(1):21–33. doi: 10.1002/ijc.28954. CrossRefGoogle Scholar
  90. 90.
    Zhang Z, Ramnath N, Nagrath S. Current status of CTCs as liquid biopsy in lung cancer and future directions. Front Oncol. 2015;5:209. doi: 10.3389/fonc.2015.00209. PubMedPubMedCentralGoogle Scholar
  91. 91.
    Corradi M, Poli D, Banda I, Bonini S, Mozzoni P, Pinelli S, et al. Exhaled breath analysis in suspected cases of non-small-cell lung cancer: a cross-sectional study. J Breath Res. 2015;9(2):027101. doi: 10.1088/1752-7155/9/2/027101. PubMedCrossRefGoogle Scholar
  92. 92.
    Peled N, Hakim M, Bunn Jr PA, Miller YE, Kennedy TC, Mattei J, et al. Non-invasive breath analysis of pulmonary nodules. J Thorac Oncol: Off Publ Int Assoc Study Lung Cancer. 2012;7(10):1528–33. doi: 10.1097/JTO.0b013e3182637d5f. CrossRefGoogle Scholar
  93. 93.
    Li J, Peng Y, Duan Y. Diagnosis of breast cancer based on breath analysis: an emerging method. Crit Rev Oncol Hematol. 2013;87(1):28–40. doi: 10.1016/j.critrevonc.2012.11.007. PubMedCrossRefGoogle Scholar
  94. 94.
    Barash O, Zhang W, Halpern JM, Hua QL, Pan YY, Kayal H, et al. Differentiation between genetic mutations of breast cancer by breath volatolomics. Oncotarget. 2015;6(42):44864–76. doi: 10.18632/oncotarget.6269. PubMedPubMedCentralGoogle Scholar
  95. 95.
    Wang C, Ke C, Wang X, Chi C, Guo L, Luo S, et al. Noninvasive detection of colorectal cancer by analysis of exhaled breath. Anal Bioanal Chem. 2014;406(19):4757–63. doi: 10.1007/s00216-014-7865-x. PubMedCrossRefGoogle Scholar
  96. 96.
    Peng G, Hakim M, Broza YY, Billan S, Abdah-Bortnyak R, Kuten A, et al. Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br J Cancer. 2010;103(4):542–51. doi: 10.1038/sj.bjc.6605810. PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    ZQ X, Broza YY, Ionsecu R, Tisch U, Ding L, Liu H, et al. A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions. Br J Cancer. 2013;108(4):941–50. doi: 10.1038/bjc.2013.44. CrossRefGoogle Scholar
  98. 98.
    Amal H, Leja M, Funka K, Skapars R, Sivins A, Ancans G, et al. Detection of precancerous gastric lesions and gastric cancer through exhaled breath. Gut. 2016;65(3):400–7. doi: 10.1136/gutjnl-2014-308536. PubMedCrossRefGoogle Scholar
  99. 99.
    Amal H, Leja M, Broza YY, Tisch U, Funka K, Liepniece-Karele I, et al. Geographical variation in the exhaled volatile organic compounds. J Breath Res. 2013;7(4):047102. doi: 10.1088/1752-7155/7/4/047102. PubMedCrossRefGoogle Scholar
  100. 100.
    Konstantinidi EM, Lappas AS, Tzortzi AS, Behrakis PK. Exhaled breath condensate: technical and diagnostic aspects. Sci World J. 2015;2015:435160. doi: 10.1155/2015/435160. CrossRefGoogle Scholar
  101. 101.
    Schmidt K, Podmore I. Current challenges in volatile organic compounds analysis as potential biomarkers of cancer. J Biomark. 2015;2015:981458. doi: 10.1155/2015/981458. PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Vo-Dinh T, Liu Y, Fales AM, Ngo H, Wang HN, Register JK, et al. SERS nanosensors and nanoreporters: golden opportunities in biomedical applications. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015;7(1):17–33. doi: 10.1002/wnan.1283. PubMedCrossRefGoogle Scholar
  103. 103.
    Lin J, Chen R, Feng S, Pan J, Li Y, Chen G, et al. A novel blood plasma analysis technique combining membrane electrophoresis with silver nanoparticle-based SERS spectroscopy for potential applications in noninvasive cancer detection. Nanomed: Nanotechnol, Biol Med. 2011;7(5):655–63. doi: 10.1016/j.nano.2011.01.012. Google Scholar
  104. 104.
    Chen Y, Chen G, Zheng X, He C, Feng S, Chen Y, et al. Discrimination of gastric cancer from normal by serum RNA based on surface-enhanced Raman spectroscopy (SERS) and multivariate analysis. Med Phys. 2012;39(9):5664–8. doi: 10.1118/1.4747269. PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Ito H, Inoue H, Hasegawa K, Hasegawa Y, Shimizu T, Kimura S, et al. Use of surface-enhanced Raman scattering for detection of cancer-related serum-constituents in gastrointestinal cancer patients. Nanomed: Nanotechnol, Biol Med. 2014;10(3):599–608. doi: 10.1016/j.nano.2013.09.006. Google Scholar
  106. 106.
    Bonifacio A, Dalla Marta S, Spizzo R, Cervo S, Steffan A, Colombatti A, et al. Surface-enhanced Raman spectroscopy of blood plasma and serum using Ag and Au nanoparticles: a systematic study. Anal Bioanal Chem. 2014;406(9–10):2355–65. doi: 10.1007/s00216-014-7622-1. PubMedCrossRefGoogle Scholar
  107. 107.
    Wang C, Yu C. Analytical characterization using surface-enhanced Raman scattering (SERS) and microfluidic sampling. Nanotechnology. 2015;26(9):092001. doi: 10.1088/0957-4484/26/9/092001. PubMedCrossRefGoogle Scholar
  108. 108.
    Zhou LY, Lin SR, Li Y, Geng QM, Ding SG, Meng LM, et al. The intrinsic fluorescence spectrum of dilute gastric juice as a novel diagnostic tool for gastric cancer. J Dig Dis. 2011;12(4):279–85. doi: 10.1111/j.1751-2980.2011.00507.x. PubMedCrossRefGoogle Scholar
  109. 109.
    Deng K, Zhou LY, Lin SR, Li Y, Chen M, Geng QM, et al. A novel approach for the detection of early gastric cancer: fluorescence spectroscopy of gastric juice. J Dig Dis. 2013;14(6):299–304. doi: 10.1111/1751-2980.12040. PubMedCrossRefGoogle Scholar
  110. 110.
    Genta RM. Screening for gastric cancer: does it make sense? Alimentary pharmacology &therapeutics. 2004;20(Suppl 2):42–7. doi: 10.1111/j.1365-2036.2004.02039.x.
  111. 111.
    Abdollahi A, Folkman J. Evading tumor evasion: current concepts and perspectives of anti-angiogenic cancer therapy. Drug Resist Updat: Rev Commentaries Antimicrob Anticancer Chemother. 2010;13(1–2):16–28. doi: 10.1016/j.drup.2009.12.001. CrossRefGoogle Scholar
  112. 112.
    Leung K. 64Cu-1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid-cyclo(CGNSNPKSC). Molecular Imaging and Contrast Agent Database (MICAD). Bethesda (MD). 2004.Google Scholar
  113. 113.
    Hui X, Han Y, Liang S, Liu Z, Liu J, Hong L, et al. Specific targeting of the vasculature of gastric cancer by a new tumor-homing peptide CGNSNPKSC. J Control Release: Off J Control Release Soc. 2008;131(2):86–93. doi: 10.1016/j.jconrel.2008.07.024. CrossRefGoogle Scholar
  114. 114.
    Xin J, Zhang X, Liang J, Xia L, Yin J, Nie Y, et al. In vivo gastric cancer targeting and imaging using novel symmetric cyanine dye-conjugated GX1 peptide probes. Bioconjug Chem. 2013;24(7):1134–43. doi: 10.1021/bc3006539. PubMedCrossRefGoogle Scholar
  115. 115.
    Mort JS, Buttle DJ. Cathepsin B. Int J Biochem Cell Biol. 1997;29(5):715–20.PubMedCrossRefGoogle Scholar
  116. 116.
    Ebert MP, Kruger S, Fogeron ML, Lamer S, Chen J, Pross M, et al. Overexpression of cathepsin B in gastric cancer identified by proteome analysis. Proteomics. 2005;5(6):1693–704. doi: 10.1002/pmic.200401030. PubMedCrossRefGoogle Scholar
  117. 117.
    Nomura T, Katunuma N. Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. J Med Investig: JMI. 2005;52(1–2):1–9.CrossRefGoogle Scholar
  118. 118.
    Dohchin A, Suzuki JI, Seki H, Masutani M, Shiroto H, Kawakami Y. Immunostained cathepsins B and L correlate with depth of invasion and different metastatic pathways in early stage gastric carcinoma. Cancer. 2000;89(3):482–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Herszenyi L, Istvan G, Cardin R, De Paoli M, Plebani M, Tulassay Z, et al. Serum cathepsin B and plasma urokinase-type plasminogen activator levels in gastrointestinal tract cancers. Eur J Cancer Prev: Off J Eur Cancer Prev Organ. 2008;17(5):438–45. doi: 10.1097/CEJ.0b013e328305a130. CrossRefGoogle Scholar
  120. 120.
    Hirano T, Manabe T, Takeuchi S. Serum cathepsin B levels and urinary excretion of cathepsin B in the cancer patients with remote metastasis. Cancer Lett. 1993;70(1–2):41–4.PubMedCrossRefGoogle Scholar
  121. 121.
    Ding S, Eric Blue R, Chen Y, Scull B, Kay Lund P, Morgan D. Molecular imaging of gastric neoplasia with near-infrared fluorescent activatable probes. Mol Imaging. 2012;11(6):507–15.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Petersen H, Holdgaard PC, Madsen PH, Knudsen LM, Gad D, Gravergaard AE, et al. FDG PET/CT in cancer: comparison of actual use with literature-based recommendations. Eur J Nucl Med Mol Imaging. 2016;43(4):695–706. doi: 10.1007/s00259-015-3217-0. PubMedCrossRefGoogle Scholar
  123. 123.
    Yun M. Imaging of gastric cancer metabolism using 18 F-FDG PET/CT. J Gastric Cancer. 2014;14(1):1–6. doi: 10.5230/jgc.2014.14.1.1. PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Dassen AE, Lips DJ, Hoekstra CJ, Pruijt JF, Bosscha K. FDG-PET has no definite role in preoperative imaging in gastric cancer. Eur J Surg Oncol: J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2009;35(5):449–55. doi: 10.1016/j.ejso.2008.11.010. CrossRefGoogle Scholar
  125. 125.
    Wu CX, Zhu ZH. Diagnosis and evaluation of gastric cancer by positron emission tomography. World J Gastroenterol: WJG. 2014;20(16):4574–85. doi: 10.3748/wjg.v20.i16.4574. PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Hopkins S, Yang GY. FDG PET imaging in the staging and management of gastric cancer. J Gastrointest Oncol. 2011;2(1):39–44. doi: 10.3978/j.issn.2078-6891.2010.004. PubMedPubMedCentralGoogle Scholar
  127. 127.
    Wilson KE, Wang TY, Willmann JK. Acoustic and photoacoustic molecular imaging of cancer. J Nucl Med: Off Publ, Soc Nucl Med. 2013;54(11):1851–4. doi: 10.2967/jnumed.112.115568. CrossRefGoogle Scholar
  128. 128.
    Xu B, Li X, Yin J, Liang C, Liu L, Qiu Z, et al. Evaluation of 68Ga-labeled MG7 antibody: a targeted probe for PET/CT imaging of gastric cancer. Sci Rep. 2015;5:8626. doi: 10.1038/srep08626. PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Guo DL, Dong M, Wang L, Sun LP, Yuan Y. Expression of gastric cancer-associated MG7 antigen in gastric cancer, precancerous lesions and H. Pylori -associated gastric diseases. World J Gastroenterol: WJG. 2002;8(6):1009–13.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Cheng CC, Huang CF, Ho AS, Peng CL, Chang CC, Mai FD, et al. Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles. Int J Nanomedicine. 2013;8:1385–91. doi: 10.2147/IJN.S42003. PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Zhu H, Zhao C, Liu F, Wang L, Feng J, Zhou Z, et al. Radiolabeling and evaluation of (64)Cu-DOTA-F56 peptide targeting vascular endothelial growth factor receptor 1 in the molecular imaging of gastric cancer. Am J Cancer Res. 2015;5(11):3301–10.PubMedPubMedCentralGoogle Scholar
  132. 132.
    Ray S, Reddy PJ, Jain R, Gollapalli K, Moiyadi A, Srivastava S. Proteomic technologies for the identification of disease biomarkers in serum: advances and challenges ahead. Proteomics. 2011;11(11):2139–61. doi: 10.1002/pmic.201000460. PubMedCrossRefGoogle Scholar
  133. 133.
    Huijbers A, Velstra B, Dekker TJ, Mesker WE, van der Burgt YE, Mertens BJ, et al. Proteomic serum biomarkers and their potential application in cancer screening programs. Int J Mol Sci. 2010;11(11):4175–93. doi: 10.3390/ijms11114175. PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of GastroenterologyThe First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and HepatologyNanchangChina

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